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Novel Localized Combination Drug Delivery Platform at the Islet Graft Site to Improve Type 1 Diabetes Treatment
Location: 44
Mentor: Dr. Dhanashree Surve
Islet transplantation offers a potential treatment for type 1 diabetes, but systemic immunosuppression remains a major barrier due to off-target toxicity and limited long-term graft protection. This project explores a localized drug delivery platform in which immunomodulator-loaded nanoparticles (NPs) are embedded in microparticles (MPs) and placed within a peptide hydrogel at the islet graft site. Two candidate drugs, apremilast (APM) and mycophenolate mofetil (MMF), are being evaluated for their distinct effects on macrophages and lymphocytes.
To support future in vitro release studies, an HPLC method was developed and validated for MMF detection, enabling accurate quantification across a clinically relevant range. In parallel, we are developing an in vitro model to mimic subcutaneous drug delivery and inform local formulation performance. Tissue-mimicking gels were prepared using various polymer blends (alginate, xanthan, carboxymethylcellulose) crosslinked at different calcium concentrations. These gels are being characterized based on swelling behavior and mechanical stability to guide formulation design.
Together, these efforts aim to inform the development of a site-specific immunosuppressive system that minimizes systemic exposure while supporting islet engraftment. The modular design allows flexibility in drug selection and release tuning, supporting a future goal of improving long-term outcomes in islet transplantation.
